In 1937 Albright and co-workers suggested that rickets or osteomalacia might result from deficient action of vitamin D. With recognition that vitamin D is the precursor to 1,25(OH)2D, a steroidal hormone, it has become possible to identify patients with defective activation or target action of 1,25(OH)2D. We have shown that some patients with hereditary resistance to 1,25(OH)2D have defective nuclear uptake of the hormone.